Affinage

CKAP5

Cytoskeleton-associated protein 5 · UniProt Q14008

Length
2032 aa
Mass
225.5 kDa
Annotated
2026-06-09
92 papers in source corpus 31 papers cited in narrative 31 extracted findings
Cross-family judge vs UniProt: Affinage preferred faithfulness: 6/6 claims corpus-supported (100%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

CKAP5 (ch-TOG/TOGp), the human homolog of XMAP215, is a microtubule-associated protein and microtubule polymerase that drives microtubule assembly at centrosomes, spindles, and growing plus ends (PMID:9570755, PMID:10766876, PMID:17178729). Mechanistically, it uses an array of TOG domains—flat, HEAT-repeat paddles whose conserved intra-repeat turns form a tubulin-binding face (PMID:17355870)—to selectively bind curved, unpolymerized αβ-tubulin via surfaces not used in lattice contacts, allowing it to discriminate free tubulin and recognize the growing tip (PMID:22904013). Polymerase activity requires multiple tubulin-binding TOG domains plus a basic lattice-binding region, with overall tubulin affinity correlating with activity; mutating tubulin contacts in any single TOG domain sharply reduces polymerization (PMID:21282620, PMID:24966168). In dividing cells, ch-TOG organizes spindle poles and protects centrosomal and kinetochore microtubules from MCAK-mediated depolymerization, acting downstream of Aurora-A in spindle pole integrity (PMID:12569123, PMID:14749730, PMID:18809577, PMID:18663358). It forms a trimeric complex with TACC3 and clathrin that builds inter-microtubule bridges within kinetochore fibers and maintains K-fiber tension; TACC3—stabilized by Aurora-A phosphorylation—recruits ch-TOG to spindle microtubules, and the TACC3 coiled-coil 'stutter' engages a sixth TOG-like region of ch-TOG (PMID:21297582, PMID:23918938, PMID:12569123, PMID:23532825). Beyond polymerase activity, ch-TOG stabilizes CENP-E at kinetochores through its TOG4–TOG5 domains to suppress attachment errors (PMID:38424231), cross-links microtubules with F-actin via its TOG5 domain to promote axon outgrowth independently of polymerase activity (PMID:39504455), and is required in oligodendrocytes to transport MBP mRNA into processes for local translation (PMID:28063167).

Mechanistic history

Synthesis pass · year-by-year structured walk · 24 steps
  1. 1998 High

    Established that the XMAP215 human homolog is a bona fide microtubule-associated protein that promotes assembly and localizes to centrosomes and spindles, defining its cellular arena.

    Evidence Microtubule co-sedimentation, immunofluorescence, and fractionation in human cells

    PMID:9570755

    Open questions at the time
    • Did not resolve which protein regions bind microtubules versus free tubulin
    • No kinetic mechanism of assembly promotion
  2. 2000 High

    Mapped functional domains, separating an N-terminal basic microtubule-binding/end-binding region from a C-terminal free-tubulin-binding region, and demonstrated the protein is essential for microtubule polymerization in mitotic extract.

    Evidence Truncation co-pelleting assays and immunodepletion/add-back in mammalian mitotic extract

    PMID:10766876 PMID:10770946

    Open questions at the time
    • Domain architecture of tubulin recognition not yet structurally defined
    • ATP-dependence of extract polymerization not mechanistically explained
  3. 2000 Medium

    Linked ch-TOG to mitotic kinase machinery by showing its C-terminal proline-rich region co-sediments cyclin B1/cdc2 with microtubules, raising the possibility it targets MPF to the cytoskeleton.

    Evidence Co-IP and fragment co-sedimentation in a single lab

    PMID:10640423

    Open questions at the time
    • Functional consequence of MPF targeting not established
    • Single-lab interaction without reciprocal in vivo validation
  4. 2002 Medium

    Identified TACC-family proteins as ch-TOG partners via its C-terminus, opening the TACC axis that would prove central to its spindle recruitment.

    Evidence Yeast two-hybrid screen with biochemical confirmation

    PMID:11903063

    Open questions at the time
    • Cellular function of the ch-TOG–TACC interaction not yet tested
    • Y2H interaction needs in vivo context
  5. 2003 High

    Defined ch-TOG's primary mitotic role as spindle pole organization and established the reciprocal dependency in which TACC3 is required to recruit ch-TOG to spindles.

    Evidence RNAi knockdown and immunofluorescence in HeLa cells

    PMID:12569123

    Open questions at the time
    • Molecular basis of TACC3-dependent recruitment not yet mapped
    • Did not distinguish polymerase from scaffolding contributions
  6. 2004 Medium

    Showed ch-TOG protects spindle microtubules from MCAK depolymerization at both poles and plus ends, defining an antagonistic balance governing spindle stability.

    Evidence Inducible overexpression and shRNA in human leukemia cells with phenotypic spindle analysis

    PMID:14749730

    Open questions at the time
    • Mechanism of MCAK antagonism unresolved
    • Single-lab phenotypic study
  7. 2006 High

    Provided the first quantitative in vitro mechanism, showing purified protein shortens nucleation, accelerates elongation, lowers critical concentration, and inhibits depolymerization.

    Evidence In vitro kinetic turbidimetry and GTPase assays with purified TOGp

    PMID:17178729

    Open questions at the time
    • Structural basis of these kinetic effects not addressed
    • Single-lab kinetic study
  8. 2007 High

    Solved the TOG domain fold, revealing a flat HEAT-repeat paddle with a conserved surface-exposed tubulin-binding face validated by mutagenesis.

    Evidence X-ray crystallography of a TOG domain plus site-directed mutagenesis of orthologs

    PMID:17355870

    Open questions at the time
    • Conformation of tubulin recognized by TOG not yet shown
    • How multiple TOGs cooperate not addressed
  9. 2008 High

    Placed ch-TOG downstream of Aurora-A in spindle pole integrity and dissected its dual roles in centrosomal microtubule production and MCAK-independent kinetochore microtubule protection.

    Evidence RNAi co-depletion epistasis and live-cell spindle imaging

    PMID:18663358 PMID:18809577

    Open questions at the time
    • Direct Aurora-A regulation of ch-TOG not demonstrated
    • Mechanistic link between centrosomal and kinetochore functions unclear
  10. 2009 Medium

    Quantified ch-TOG's contribution to spindle microtubule turnover and kinetochore oscillation, showing it acts on turnover and regrowth rather than EB1-tracked plus-end growth rate.

    Evidence siRNA with FRAP, EB1 tracking, and nocodazole washout in human cells

    PMID:19373773

    Open questions at the time
    • Discrepancy with in vitro elongation effects not reconciled
    • Single-lab live-cell study
  11. 2011 High

    Established the ch-TOG/TACC3/clathrin trimeric complex as the structural inter-microtubule bridges of kinetochore fibers, and defined the multi-TOG-plus-basic-region requirement for polymerase activity.

    Evidence Reciprocal Co-IP with immunogold EM, plus systematic TOG-domain mutagenesis with in vitro polymerization assays

    PMID:21282620 PMID:21297582

    Open questions at the time
    • Stoichiometry and architecture of the bridge complex not fully resolved
    • How TOG affinity quantitatively translates to processivity unaddressed
  12. 2012 High

    Captured the catalytic basis of conformation selectivity by crystallizing a TOG domain bound to curved αβ-tubulin, and showed ch-TOG occupies a distinct plus-end zone beyond EB1.

    Evidence X-ray co-crystal structure of TOG1:αβ-tubulin and high-resolution plus-end localization microscopy

    PMID:22904013 PMID:23251535

    Open questions at the time
    • How conformation-selective binding drives net polymerization in cells not shown
    • Functional division of labor between ch-TOG and EB1 zones partly inferred
  13. 2012 Medium

    Defined clathrin as an upstream stabilizer of ch-TOG protein levels and centrosomal localization, linking S-phase clathrin function and Aurora-A to centrosome integrity.

    Evidence RNAi, SNAP-tag chemical inactivation, and Aurora-A inhibition with live-cell imaging

    PMID:22891263

    Open questions at the time
    • Mechanism by which clathrin stabilizes ch-TOG protein unknown
    • Single-lab study
  14. 2013 High

    Mapped the molecular interaction surfaces of the TACC3/ch-TOG/clathrin complex and dissected its requirement for kinetochore-fiber tension and checkpoint satisfaction rather than microtubule number.

    Evidence Truncation/mutagenesis interaction mapping plus knocksideways acute inactivation with checkpoint assays

    PMID:23532825 PMID:23918938

    Open questions at the time
    • Physical basis of tension generation by the bridges not established
    • Whether the proposed TOG6/stutter interaction is a true sixth TOG domain unresolved
  15. 2014 High

    Showed the TOG array is functionally non-redundant, with structurally distinct domains (e.g., bent TOG4) and differential tubulin affinities, each individually required for full polymerase rescue.

    Evidence X-ray crystallography of ch-TOG TOG4, in vitro binding, and S2 cell rescue with point mutants

    PMID:24966168

    Open questions at the time
    • How distinct TOG geometries are spatially arranged at the tip not shown
    • Specific tubulin-conformation engaged by TOG4 inferred from structure
  16. 2015 Medium

    Revealed a clathrin- and Aurora-A-independent TACC3–ch-TOG pool that tracks microtubule plus ends, and tied ch-TOG plus-end activity to cancer cell migration sensitive to eribulin.

    Evidence Mutational analysis with live-cell plus-end tracking, and siRNA with chemotaxis and microtubule dynamics assays

    PMID:25596274 PMID:26497677

    Open questions at the time
    • Relative contributions of complexed versus free ch-TOG pools to dynamics unresolved
    • Single-lab studies
  17. 2016 High

    Identified a conserved Ndc80-kinetochore interaction and showed the ortholog can both stabilize and destabilize kinetochore-microtubule attachments in a tension- and tip-state-dependent manner, separate from polymerase activity.

    Evidence Reconstituted kinetochore-microtubule attachment assay with force measurements and genetics in yeast, with conserved interaction shown for ch-TOG

    PMID:27156448

    Open questions at the time
    • Whether human ch-TOG recapitulates the bidirectional attachment behavior in cells not directly tested
    • Molecular switch governing stabilize-vs-destabilize unresolved
  18. 2017 High

    Uncovered a non-mitotic role in which ch-TOG transports MBP mRNA into oligodendrocyte processes for local translation, revealing a post-transcriptional function in myelination.

    Evidence Conditional knockout in mice with in situ hybridization, immunoblotting, and EM of myelin

    PMID:28063167

    Open questions at the time
    • Mechanism linking ch-TOG to mRNA cargo transport not defined
    • Whether this depends on polymerase or scaffolding activity unknown
  19. 2018 High

    Proposed a polymerase assembly model in which TOG arrays form square pseudo-dimeric assemblies positioning four unpolymerized tubulins that unfurl to drive concerted protofilament polymerization.

    Evidence X-ray crystallography, crosslinking, EM, and mutagenesis of the fission yeast ortholog

    PMID:30422110

    Open questions at the time
    • Whether human ch-TOG forms equivalent square assemblies not directly shown
    • Unfurling step not captured in real time
  20. 2023 Medium

    Showed the TACC3–ch-TOG interaction spatially regulates γ-TuRC-dependent nucleation, restraining γ-tubulin on spindle microtubules versus centrosomes.

    Evidence TACC3 deletion mutants, Co-IP, and γ-TuRC localization quantification in human cells

    PMID:36790370

    Open questions at the time
    • Direct effect of ch-TOG on γ-TuRC activity not measured
    • Single-lab study
  21. 2024 High

    Defined a polymerase-independent kinetochore function in which TOG4–TOG5 stabilizes CENP-E via CENP-E-BubR1 binding and antagonizes PP1, suppressing attachment errors.

    Evidence siRNA, TOG4-TOG5 domain rescue, Co-IP, PP1 localization, and phosphomimetic analysis in human cells

    PMID:38424231

    Open questions at the time
    • Direct structural basis of TOG4-TOG5/CENP-E-BubR1 binding not solved
    • How this role coordinates with polymerase activity unclear
  22. 2024 High

    Established a TOG5-mediated actin-binding/bundling activity that cross-links microtubules with F-actin, polymerase-independent, to drive growth-cone alignment and axon outgrowth.

    Evidence In vitro TIRF reconstitution with domain mutants and Xenopus neuronal growth-cone imaging

    PMID:39504455

    Open questions at the time
    • Structural basis of TOG5 actin binding not solved
    • How MT/F-actin cross-linking is regulated in vivo unknown
  23. 2025 High

    Structurally characterized the ch-TOG α-helical bundle that binds TACC3 and showed selective disruption of this interface fragments pericentriolar material and delays mitosis, defining a PCM-integrity role.

    Evidence Crystallography/modeling with Affimer-mediated inhibition in live human cells

    PMID:40105698

    Open questions at the time
    • How TACC3–ch-TOG maintains PCM integrity mechanistically unresolved
    • Single-lab study
  24. 2025 Medium

    Quantitatively modeled the polymerase as a tubulin-shuttling antenna with enzyme-like, saturable kinetics whose end occupancy is concentration-independent, limited by tubulin:TOG association.

    Evidence In vitro microtubule dynamics with kinetic modeling and TOG:tubulin binding measurements (preprint)

    PMID:bio_10.1101_2025.06.09.658552

    Open questions at the time
    • Not yet peer reviewed
    • Whether human ch-TOG shares identical kinetics not directly shown

Open questions

Synthesis pass · forward-looking unresolved questions
  • How CKAP5's distinct activities—polymerase, kinetochore-attachment regulation, MT/F-actin cross-linking, and mRNA transport—are coordinated and switched within a single cell remains unresolved.
  • No unified model integrating polymerase versus scaffolding/transport functions
  • Regulatory inputs (phosphorylation, partner availability) that toggle between modes not mapped
  • Mechanism of MBP mRNA cargo recognition unknown

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0140096 catalytic activity, acting on a protein 4 GO:0008092 cytoskeletal protein binding 3 GO:0060090 molecular adaptor activity 3 GO:0003723 RNA binding 1
Localization
GO:0005815 microtubule organizing center 5 GO:0005856 cytoskeleton 3 GO:0005634 nucleus 1 GO:0005783 endoplasmic reticulum 1
Pathway
R-HSA-1640170 Cell Cycle 4 R-HSA-1266738 Developmental Biology 2 R-HSA-1852241 Organelle biogenesis and maintenance 2
Partners
AURKABUBR1CENP-ECLTCMCAKNDC80TACC1TACC3
Complex memberships
TACC3/ch-TOG/clathrin complexkinetochore fiber inter-microtubule bridges

Evidence

Reading pass · 31 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
1998 TOGp (CKAP5) is a microtubule-associated protein that co-sediments with taxol-stabilized microtubules in vitro, promotes microtubule assembly both in solution and from nucleation centers, and localizes to centrosomes and spindles in mitotic cells (ER during interphase), establishing it as the human homolog of XMAP215. Microtubule co-sedimentation assay, immunofluorescence microscopy, subcellular fractionation Journal of cell science High 9570755
2000 The microtubule-binding domain of TOGp resides in a basic ~600 amino acid region near the N-terminus; full-length TOGp shows enhanced binding to microtubule ends and binds along individual protofilaments; the C-terminal region binds free tubulin dimer with low affinity. Microtubule co-pelleting assay with truncation constructs expressed in reticulocyte lysate The Journal of biological chemistry High 10770946
2000 ch-TOGp is required for microtubule aster formation and robust microtubule polymerization in a mammalian mitotic extract; immunodepletion of ch-TOGp severely inhibits microtubule polymerization in an ATP-dependent manner. Immunodepletion from mammalian mitotic extract, microtubule aster assembly assay The Journal of biological chemistry High 10766876
2000 TOG/XMAP215 associates with cyclin B1 and p34cdc2 kinase; the C-terminal proline-rich region of TOG is sufficient to co-sediment cyclin B1 with microtubules; this interaction may target MPF to the microtubule cytoskeleton during mitosis. Co-immunoprecipitation, microtubule co-sedimentation with recombinant fragments, immunofluorescence co-localization Experimental cell research Medium 10640423
2002 ch-TOG interacts with TACC1 through the C-terminus of ch-TOG, as identified by yeast two-hybrid screening and confirmed biochemically, suggesting ch-TOG participates in multiple TACC protein complexes. Yeast two-hybrid screen, biochemical interaction assay The Biochemical journal Medium 11903063
2003 RNAi depletion of ch-TOG in HeLa cells causes highly disorganized spindles with disorganized spindle poles; ch-TOG plays a major role in organizing spindle poles and a minor role in stabilizing spindle microtubules. TACC3 depletion mislocalizes ch-TOG from spindle microtubules, indicating TACC3 is required to recruit ch-TOG to centrosomes/spindles. RNA interference (RNAi) in HeLa cells, immunofluorescence microscopy Genes & development High 12569123
2004 ch-TOG (TOGp) protects spindle microtubules from MCAK-mediated depolymerization at the centrosome to prevent multipolar spindles; TOGp also has an MCAK-independent role in protecting spindle MTs from MCAK at plus ends during mitosis. Inducible overexpression and shRNA knockdown in human leukemia cells, phenotypic spindle analysis The EMBO journal Medium 14749730
2006 Purified TOGp shortens the nucleation phase of microtubule assembly, increases the apparent first-order rate constant of elongation, decreases tubulin critical concentration, and inhibits depolymerization during steady state — mechanistically acting as a promoter of both nucleation and elongation. In vitro kinetic analysis of tubulin polymerization with purified TOGp, turbidimetry, GTPase activity assay The Journal of biological chemistry High 17178729
2007 Crystal structure of a TOG domain (from C. elegans Zyg9) reveals a flat, paddle-like structure of six HEAT-repeat elements; the intra-HEAT repeat turns form a conserved, surface-exposed tubulin-binding face; mutagenesis of conserved residues in the TOG1 domain of Stu2p (yeast CKAP5 homolog) confirmed these turns participate in tubulin contact. X-ray crystallography (1.9 Å), site-directed mutagenesis of tubulin-binding residues Structure High 17355870
2008 Aurora-A depletion causes ch-TOG to abnormally accumulate at spindle poles and MCAK to delocalize from poles; co-depletion of Aurora-A and ch-TOG mitigates the fragmented pole phenotype caused by Aurora-A loss, placing ch-TOG downstream of Aurora-A in spindle pole integrity control. RNAi co-depletion (Aurora-A and ch-TOG), immunofluorescence, genetic epistasis Oncogene Medium 18663358
2008 ch-TOG is required to produce/maintain long centrosomal microtubules after nuclear envelope breakdown and for proper microtubule dynamics at centrosomes; additionally, ch-TOG protects kinetochore microtubules from MCAK depolymerization. The centrosomal microtubule assembly function is independent of MCAK activity (co-depletion of MCAK does not rescue centrosomal MT defects). RNAi knockdown, co-depletion of ch-TOG and MCAK, real-time spindle assembly imaging Molecular and cellular biology High 18809577
2009 TOGp depletion by siRNA slows spindle microtubule turnover ~2-fold (measured by FRAP of GFP-tubulin) and reduces microtubule regrowth after nocodazole washout at centrosomes and near chromatin, without affecting EB1-tracked plus-end growth rates; kinetochore oscillations during prometaphase/metaphase are also reduced. siRNA knockdown, FRAP of GFP-tubulin, EB1-GFP plus-end tracking, nocodazole washout assay Cell motility and the cytoskeleton Medium 19373773
2010 Integrin-linked kinase (ILK) regulates centrosome clustering in cancer cells through ch-TOG and TACC3; ILK performs centrosome clustering activity in a focal adhesion-independent, centrosome-dependent manner via these microtubule-regulating proteins. A specific TACC3 phosphorylation is required and ILK regulates it via Aurora-A. RNAi knockdown, live-cell imaging, ILK inhibition, phosphorylation analysis Oncogene Medium 20838383
2011 ch-TOG, TACC3, and clathrin form a trimeric complex that constitutes inter-microtubule bridges in kinetochore fibers; TACC3 and ch-TOG anchor the complex to spindle microtubules; clathrin depletion or TACC3 depletion causes loss of short inter-MT bridges and general loss of kinetochore fiber microtubules; immunogold labeling confirmed clathrin in inter-MT bridges. Co-immunoprecipitation, electron microscopy ultrastructural analysis, immunogold labeling, RNAi knockdown The EMBO journal High 21297582
2011 XMAP215 polymerase activity requires multiple tubulin-binding TOG domains plus a basic lattice-binding region; individual TOG domains differentially contribute to overall tubulin affinity, and overall affinity correlates with polymerase activity; an engineered 'bonsai' protein with two TOG domains and the basic region retains near-full polymerase activity. Site-directed mutagenesis of TOG domains, in vitro microtubule polymerization assays, tubulin binding assays Proceedings of the National Academy of Sciences High 21282620
2012 Crystal structure of Stu2p TOG1 bound to yeast αβ-tubulin shows TOG1 binds curved (unpolymerized) αβ-tubulin conformation; TOG1 contacts α- and β-tubulin surfaces that do not participate in microtubule assembly; this conformation-selective binding explains how TOG polymerases discriminate unpolymerized from polymerized tubulin and recognize the growing microtubule end. X-ray crystallography of TOG1:αβ-tubulin complex Science High 22904013
2012 ch-TOG accumulation sites at microtubule plus ends protrude ~100 nm beyond EB1 comets, indicating ch-TOG and EB1 recognize distinct regions at growing microtubule ends; ch-TOG and EB1 additively increase microtubule dynamicity but only EB1 exhibits microtubule-cell cortex attachment activity. High-resolution (TIRF/SIM) microscopy, overexpression in interphase HeLa cells PloS one Medium 23251535
2012 Clathrin (CHC17 isoform) stabilizes ch-TOG protein levels and promotes its localization to metaphase centrosomes; clathrin inactivation during S phase reduces both clathrin and ch-TOG at metaphase centrosomes, causing centrosome fragmentation, phenocopied by Aurora A inhibition, placing clathrin upstream of ch-TOG centrosomal stabilization. RNAi depletion, chemical SNAP-tag inactivation, Aurora A inhibitor (MLN8237), live-cell imaging The Journal of cell biology Medium 22891263
2013 Within the TACC3/ch-TOG/clathrin complex, TACC3 and clathrin are interdependent for spindle recruitment; the N-terminal domain of clathrin and the TACC domain of TACC3 form a cooperative microtubule interaction surface; a dileucine motif and Aurora A-phosphorylated S558 on TACC3 bind clathrin; a proposed sixth TOG domain (stutter in TACC3 coiled-coil interacts with ch-TOG TOG6) is required for microtubule localization of ch-TOG but not TACC3-clathrin. Interaction mapping by truncation/mutagenesis, Co-IP, microtubule binding assays, live-cell localization The Journal of cell biology High 23918938
2013 Rapid removal of TACC3/ch-TOG/clathrin complex from kinetochore fibers at metaphase (using 'knocksideways') reduces kinetochore fiber tension and prevents spindle checkpoint satisfaction without significant loss of kinetochore fiber microtubule number, indicating the complex is required for maintenance of K-fiber tension rather than microtubule stability per se. Knocksideways rapid inactivation, live-cell imaging, inter-kinetochore distance measurement, spindle checkpoint assay Journal of cell science High 23532825
2014 Crystal structures of ch-TOG TOG4 reveal a conserved domain bend architecturally distinct from TOG1 and TOG2, predicting novel engagement with α-tubulin; in vitro assays show differential tubulin-binding affinities across the TOG array; mutating tubulin-binding determinants in any single TOG domain dramatically reduces rescue of microtubule polymerization. X-ray crystallography of ch-TOG TOG4, in vitro tubulin binding assays, S2 cell rescue assay with point mutants Molecular biology of the cell High 24966168
2015 TACC3 tracks plus-ends of microtubules via its interaction with ch-TOG, independently of EB1, EB3, Aurora-A phosphorylation, and clathrin binding; this defines a clathrin-independent pool of TACC3-ch-TOG at microtubule plus ends. Mutational analysis, live-cell fluorescence microscopy, co-immunoprecipitation Biology open Medium 25596274
2015 ch-TOG is required for directed cancer cell migration; eribulin depletes ch-TOG from microtubule plus ends, decreasing microtubule growth speed and cortical stabilization; ch-TOG knockdown phenocopies eribulin effects on microtubule dynamics and chemotaxis. siRNA knockdown of ch-TOG, live-cell microtubule dynamics imaging, chemotaxis assay Oncotarget Medium 26497677
2016 Stu2 (yeast CKAP5 ortholog) interacts with the Ndc80 kinetochore complex and its human ortholog ch-TOG shares this conserved interaction; Stu2 can stabilize or destabilize kinetochore-microtubule attachments depending on tension level and whether the microtubule tip is assembling or disassembling, independent of its regulation of microtubule dynamics. Reconstituted kinetochore-microtubule attachment assay, force measurements, biochemical pulldowns, genetic analysis Cell High 27156448
2017 Conditional knockout of TOG (CKAP5) in myelinating glia causes severe CNS hypomyelination and reduced MBP protein without affecting MBP mRNA levels; in TOG KO oligodendrocytes, MBP mRNA is confined to cell bodies rather than being transported into processes/myelin compartment, indicating TOG is required for MBP mRNA transport to sites of translation. Conditional knockout in mice, in situ hybridization for MBP mRNA, immunoblotting, electron microscopy of myelin Glia High 28063167
2018 Structural and biochemical studies of Alp14 (fission yeast CKAP5 ortholog) TOG array show it binds four tubulins via dimeric TOG1-TOG2 subunits arranged in square assemblies; an X-ray structure reveals square-shaped pseudo-dimeric assemblies positioning four unpolymerized tubulins in a polarized wheel-like configuration; an 'unfurled' assembly binds two polymerized tubulins, supporting a model in which square assemblies unfurl to facilitate concerted tubulin polymerization into protofilaments. X-ray crystallography, crosslinking, electron microscopy, biochemical mutagenesis eLife High 30422110
2023 TACC3-ch-TOG interaction controls TACC3 phosphorylation and TACC3-mediated stabilization of γ-TuRC at centrosomes; deletion of the ch-TOG-binding region in TACC3 enhances γ-TuRC recruitment to centrosomes; ch-TOG depletion increases γ-tubulin localization on spindle microtubules without affecting centrosomal γ-tubulin, indicating ch-TOG controls spatial regulation of γ-TuRC-dependent microtubule nucleation. TACC3 deletion mutants, co-immunoprecipitation, immunofluorescence quantification of γ-TuRC localization in human cells Bioscience reports Medium 36790370
2024 CKAP5 stabilizes CENP-E at kinetochores in human cells; CKAP5 depletion impairs CENP-E localization at metaphase kinetochores, increases kinetochore-microtubule stability, and causes attachment errors; the TOG4-TOG5 domain of CKAP5 mediates interaction with CENP-E-BubR1 and rescues CENP-E kinetochore localization; CKAP5 depletion facilitates PP1 recruitment to kinetochores, and a PP1 target site-specific CENP-E phosphomimetic mutant is stabilized at kinetochores in CKAP5-depleted cells. siRNA knockdown, domain rescue (TOG4-TOG5 fragment), co-immunoprecipitation (CENP-E-BubR1), PP1 localization assay, phosphomimetic mutant analysis, computational modeling EMBO reports High 38424231
2024 The TOG5 domain of CKAP5 is necessary for binding and bundling actin filaments and for cross-linking microtubules with F-actin in vitro; this MT/F-actin cross-linking function does not require microtubule polymerase activity; in neuronal growth cones, CKAP5 requires both MT and F-actin binding (but not MT polymerization) to promote MT-F-actin alignment and axon outgrowth. In vitro TIRF reconstitution with purified proteins, TOG5 deletion/mutation, MT/F-actin co-sedimentation and bundling assays, Xenopus neuronal growth cone live imaging Molecular biology of the cell High 39504455
2025 The α-helical bundle domain of ch-TOG that mediates interaction with TACC3 was structurally characterized; inhibition of the TACC3-ch-TOG interaction (using Affimer tools that displace ch-TOG without affecting spindle localization of other complex components) causes fragmentation of pericentriolar material in metaphase cells and delays mitotic progression, revealing a role for TACC3-ch-TOG in maintaining pericentriolar material integrity. X-ray crystallography/structural modeling, biophysical assays, Affimer-mediated inhibition in live cells, immunofluorescence The Journal of cell biology High 40105698
2025 Stu2 (yeast CKAP5 ortholog) displays enzyme-like hyperbolic dependence of microtubule growth rate on tubulin concentration; the amount of Stu2 on the microtubule end does not vary with tubulin concentration; TOG:tubulin binding is high affinity (~10 nM) with slow dissociation (~0.03 s⁻¹); Stu2 operates as a tubulin-shuttling antenna on the microtubule end, primarily limited by the rate of tubulin:TOG association. In vitro microtubule dynamics assay with quantitative kinetic modeling, TOG:tubulin binding measurements bioRxivpreprint Medium bio_10.1101_2025.06.09.658552

Source papers

Stage 0 corpus · 92 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2003 The ch-TOG/XMAP215 protein is essential for spindle pole organization in human somatic cells. Genes & development 227 12569123
2012 A TOG:αβ-tubulin complex structure reveals conformation-based mechanisms for a microtubule polymerase. Science (New York, N.Y.) 197 22904013
1998 The TOGp protein is a new human microtubule-associated protein homologous to the Xenopus XMAP215. Journal of cell science 160 9570755
2016 A TOG Protein Confers Tension Sensitivity to Kinetochore-Microtubule Attachments. Cell 144 27156448
2011 A TACC3/ch-TOG/clathrin complex stabilises kinetochore fibres by inter-microtubule bridging. The EMBO journal 132 21297582
2011 XMAP215 polymerase activity is built by combining multiple tubulin-binding TOG domains and a basic lattice-binding region. Proceedings of the National Academy of Sciences of the United States of America 126 21282620
2001 Fission yeast ch-TOG/XMAP215 homologue Alp14 connects mitotic spindles with the kinetochore and is a component of the Mad2-dependent spindle checkpoint. The EMBO journal 126 11432827
2007 Crystal structure of a TOG domain: conserved features of XMAP215/Dis1-family TOG domains and implications for tubulin binding. Structure (London, England : 1993) 104 17355870
2011 Ndc80 internal loop interacts with Dis1/TOG to ensure proper kinetochore-spindle attachment in fission yeast. Current biology : CB 88 21256022
2000 The interaction of TOGp with microtubules and tubulin. The Journal of biological chemistry 88 10770946
2021 Circular RNA ZNF609/CKAP5 mRNA interaction regulates microtubule dynamics and tumorigenicity. Molecular cell 87 34942120
2001 Dis1/TOG universal microtubule adaptors - one MAP for all? Journal of cell science 82 11719547
2004 Differential functional interplay of TOGp/XMAP215 and the KinI kinesin MCAK during interphase and mitosis. The EMBO journal 79 14749730
2010 A critical role of integrin-linked kinase, ch-TOG and TACC3 in centrosome clustering in cancer cells. Oncogene 78 20838383
2004 Interdependency of fission yeast Alp14/TOG and coiled coil protein Alp7 in microtubule localization and bipolar spindle formation. Molecular biology of the cell 69 14742702
2013 Coordination of adjacent domains mediates TACC3-ch-TOG-clathrin assembly and mitotic spindle binding. The Journal of cell biology 68 23918938
2013 Specific removal of TACC3-ch-TOG-clathrin at metaphase deregulates kinetochore fiber tension. Journal of cell science 65 23532825
2008 Aurora-A and ch-TOG act in a common pathway in control of spindle pole integrity. Oncogene 52 18663358
2012 Dissecting the nanoscale distributions and functions of microtubule-end-binding proteins EB1 and ch-TOG in interphase HeLa cells. PloS one 51 23251535
2009 The role of TOG domains in microtubule plus end dynamics. Biochemical Society transactions 49 19754440
2017 TOG-tubulin binding specificity promotes microtubule dynamics and mitotic spindle formation. The Journal of cell biology 47 28512144
2015 Crescerin uses a TOG domain array to regulate microtubules in the primary cilium. Molecular biology of the cell 47 26378256
2008 MCAK-independent functions of ch-Tog/XMAP215 in microtubule plus-end dynamics. Molecular and cellular biology 47 18809577
2013 The transporter-opsin-G protein-coupled receptor (TOG) superfamily. The FEBS journal 46 23981446
2012 Clathrin promotes centrosome integrity in early mitosis through stabilization of centrosomal ch-TOG. The Journal of cell biology 44 22891263
2014 The XMAP215 family drives microtubule polymerization using a structurally diverse TOG array. Molecular biology of the cell 42 24966168
2013 The internal loop of fission yeast Ndc80 binds Alp7/TACC-Alp14/TOG and ensures proper chromosome attachment. Molecular biology of the cell 40 23427262
2012 Microtubule plus-end tracking proteins SLAIN1/2 and ch-TOG promote axonal development. The Journal of neuroscience : the official journal of the Society for Neuroscience 40 23077057
2002 Interaction of the transforming acidic coiled-coil 1 (TACC1) protein with ch-TOG and GAS41/NuBI1 suggests multiple TACC1-containing protein complexes in human cells. The Biochemical journal 40 11903063
2015 TACC3-ch-TOG track the growing tips of microtubules independently of clathrin and Aurora-A phosphorylation. Biology open 38 25596274
2000 The Xenopus XMAP215 and its human homologue TOG proteins interact with cyclin B1 to target p34cdc2 to microtubules during mitosis. Experimental cell research 36 10640423
2009 TOGp regulates microtubule assembly and density during mitosis and contributes to chromosome directional instability. Cell motility and the cytoskeleton 35 19373773
2018 Structural basis of tubulin recruitment and assembly by microtubule polymerases with tumor overexpressed gene (TOG) domain arrays. eLife 34 30422110
2011 Aurora A kinase activity is required for localization of TACC3/ch-TOG/clathrin inter-microtubule bridges. Communicative & integrative biology 32 21966557
2018 An isolated CLASP TOG domain suppresses microtubule catastrophe and promotes rescue. Molecular biology of the cell 30 29851564
2015 CLASP2 Has Two Distinct TOG Domains That Contribute Differently to Microtubule Dynamics. Journal of molecular biology 29 26003921
2013 Microtubules and Alp7-Alp14 (TACC-TOG) reposition chromosomes before meiotic segregation. Nature cell biology 27 23770679
2006 Kinetic analysis of tubulin assembly in the presence of the microtubule-associated protein TOGp. The Journal of biological chemistry 26 17178729
2000 ch-TOGp is required for microtubule aster formation in a mammalian mitotic extract. The Journal of biological chemistry 26 10766876
2016 An unconventional interaction between Dis1/TOG and Mal3/EB1 in fission yeast promotes the fidelity of chromosome segregation. Journal of cell science 25 27872152
2023 Therapeutic gene silencing of CKAP5 leads to lethality in genetically unstable cancer cells. Science advances 21 37018392
2016 Alp7/TACC-Alp14/TOG generates long-lived, fast-growing MTs by an unconventional mechanism. Scientific reports 21 26864000
2014 CDK-dependent phosphorylation of Alp7-Alp14 (TACC-TOG) promotes its nuclear accumulation and spindle microtubule assembly. Molecular biology of the cell 20 24790093
2007 Hsp90 is required to localise cyclin B and Msps/ch-TOG to the mitotic spindle in Drosophila and humans. Journal of cell science 20 17376965
2015 Eribulin targets a ch-TOG-dependent directed migration of cancer cells. Oncotarget 19 26497677
2020 Roles of TOG and jelly-roll domains of centrosomal protein CEP104 in its functions in cilium elongation and Hedgehog signaling. The Journal of biological chemistry 13 32820051
2020 Risk factors of radiation pneumonitis in patients with NSCLC treated with concomitant chemoradiotherapy--Are we underestimating diabetes?--Turkish oncology group (TOG)/Lung cancer study group. The clinical respiratory journal 12 32470205
2021 The short flagella 1 (SHF1) gene in Chlamydomonas encodes a Crescerin TOG-domain protein required for late stages of flagellar growth. Molecular biology of the cell 11 34818077
2013 The structure of the TOG-like domain of Drosophila melanogaster Mast/Orbit. Acta crystallographica. Section F, Structural biology and crystallization communications 11 23832196
1996 Expression of the tumor over-expressed ch-TOG gene in human and baboon brain. Neuroscience letters 11 8832653
2025 CKAP5 deficiency induces premature ovarian insufficiency. EBioMedicine 10 40252251
2022 CircPDSS1 promotes the proliferation, invasion, migration, and EMT of breast cancer cell via regulating miR-320c/CKAP5 axis. Cancer cell international 10 35902921
2015 A sensitised RNAi screen reveals a ch-TOG genetic interaction network required for spindle assembly. Scientific reports 10 26037491
2015 TOG Proteins Are Spatially Regulated by Rac-GSK3β to Control Interphase Microtubule Dynamics. PloS one 10 26406596
2017 Conditional knockout of TOG results in CNS hypomyelination. Glia 9 28063167
2024 CKAP5 stabilizes CENP-E at kinetochores by regulating microtubule-chromosome attachments. EMBO reports 8 38424231
2022 ZYG-9ch-TOG promotes the stability of acentrosomal poles via regulation of spindle microtubules in C. elegans oocyte meiosis. PLoS genetics 8 36449516
2019 Kinesin-8 and Dis1/TOG collaborate to limit spindle elongation from prophase to anaphase A for proper chromosome segregation in fission yeast. Journal of cell science 8 31427431
2019 Two XMAP215/TOG Microtubule Polymerases, Alp14 and Dis1, Play Non-Exchangeable, Distinct Roles in Microtubule Organisation in Fission Yeast. International journal of molecular sciences 8 31618856
2015 Encoding the microtubule structure: Allosteric interactions between the microtubule +TIP complex master regulators and TOG-domain proteins. Cell cycle (Georgetown, Tex.) 8 25895033
2024 The efficacy of palbociclib and ribociclib in the first-line treatment of metastatic hormone receptor-positive, human epidermal growth factor receptor 2-negative breast cancer in male patients: a Turkish oncology group (TOG) study. International journal of clinical oncology 7 38310597
2023 TACC3-ch-TOG interaction regulates spindle microtubule assembly by controlling centrosomal recruitment of γ-TuRC. Bioscience reports 7 36790370
2019 Microtubule polymerase and processive plus-end tracking functions originate from distinct features within TOG domain arrays. Molecular biology of the cell 7 30969896
2018 The TOG protein Stu2/XMAP215 interacts covalently and noncovalently with SUMO. Cytoskeleton (Hoboken, N.J.) 7 29729126
2018 A Cytoskeletal Symphony: Owed to TOG. Developmental cell 7 29974863
2024 Efficacy of first-line CDK 4-6 inhibitors in premenopausal patients with metastatic breast cancer and the effect of dose reduction due to treatment-related neutropenia on efficacy: a Turkish Oncology Group (TOG) study. Journal of chemotherapy (Florence, Italy) 5 38497444
2022 The TOG protein Stu2 is regulated by acetylation. PLoS genetics 5 36084134
2021 Real-life comparison of the afatinib and first-generation tyrosine kinase inhibitors in nonsmall cell lung cancer harboring EGFR exon 19 deletion: a Turk Oncology Group (TOG) study. Journal of cancer research and clinical oncology 5 33433657
2024 Activity of CDK4/6 inhibitors and parameters affecting survival in elderly patients in age-subgroups: Turkish Oncology Group (TOG) retrospective study. BMC cancer 4 39736618
2023 An unconventional TOG domain is required for CLASP localization. Current biology : CB 4 37516114
2021 The Real-Life Data of BRAF Mutation on the Treatment of Colorectal Cancer: a TOG Study. Journal of gastrointestinal cancer 4 32914373
2021 The Relationship Between Plexin C1 Overexpression and Survival in Hepatocellular Carcinoma: a Turkish Oncology Group (TOG) Study. Journal of gastrointestinal cancer 4 33656690
2017 Purification of native M. vogae and H. contortus tubulin by TOG affinity chromatography. Experimental parasitology 4 28942049
2016 Using Interferon Alfa Before Tyrosine Kinase Inhibitors May Increase Survival in Patients With Metastatic Renal Cell Carcinoma: A Turkish Oncology Group (TOG) Study. Clinical genitourinary cancer 4 27236771
2025 Real-World Treatment Efficacy of Ribociclib or Palbociclib Plus Fulvestrant in Hormone Receptor-Positive/HER2-Negative Metastatic Breast Cancer: Turkish Oncology Group (TOG) Study. Clinical breast cancer 3 40190010
2025 Efficacy of Immunotherapy Versus Chemotherapy in Advanced Pleural Mesothelioma: A Turkish Oncology Group (TOG) Study. Medicina (Kaunas, Lithuania) 3 40282929
2024 Male meiotic spindle poles are stabilized by TACC3 and cKAP5/chTOG differently from female meiotic or somatic mitotic spindles in mice. Scientific reports 3 38413710
2024 Efficacy of everolimus plus hormonal treatment after cyclin-dependent kinase inhibitor; real-life experience, A TOG study. Breast cancer research and treatment 3 39123071
2024 The TOG5 domain of CKAP5 is required to interact with F-actin and promote microtubule advancement in neurons. Molecular biology of the cell 3 39504455
2022 Real-life comparison of afatinib and erlotinib in non-small cell lung cancer with rare EGFR exon 18 and exon 20 mutations: a Turkish Oncology Group (TOG) study. Journal of cancer research and clinical oncology 3 35381885
2021 Real-Life Analysis of Efficacy and Safety of Everolimus Plus Exemestane in Hormone Receptor-Positive, Human Epidermal Growth Factor Receptor-2-Negative Metastatic Breast Cancer Patients: A Turkish Oncology Group (TOG) Study. Cancer investigation 3 34894960
2025 Structural characterization and inhibition of the interaction between ch-TOG and TACC3. The Journal of cell biology 2 40105698
2025 CKAP5 promotes progression and cisplatin resistance in esophageal squamous cell carcinoma via microtubule-mediated YAP activation. Life sciences 2 40404119
2022 Fission yeast Dis1 is an unconventional TOG/XMAP215 that induces microtubule catastrophe to drive chromosome pulling. Communications biology 2 36435910
2020 12-Oxo-10-glutathionyl-5,8,14-eicosatrienoic acid (TOG10), a novel glutathione-containing eicosanoid generated via the 12-lipoxygenase pathway in human platelets. Prostaglandins & other lipid mediators 2 33172790
2025 Molecular Guardians of Oocyte Maturation: A Systematic Review on TUBB8, KIF11, and CKAP5 in IVF Outcomes. International journal of molecular sciences 1 40650169
2025 Efficacy of Anti-VEGF and Anti-EGFRs in Microsatellite Instable (MSI-H) Metastatic Colorectal Cancer in a Turkish Oncology Group (TOG) Cohort Study. Current oncology (Toronto, Ont.) 1 41294701
2023 The efficacy of immunotherapy and chemoimmunotherapy in patients with advanced rare tumors: A Turkish oncology group (TOG) study. Cancer medicine 1 38140782
2026 NAT10 and E2F1 Orchestrate CKAP5-Mediated Progression in Esophageal Squamous Cell Carcinoma. Journal of gastroenterology and hepatology 0 41735227
2026 Clinical Significance of Achieving No Evidence of Disease in HER2-Positive Metastatic Breast Cancer: A Multicenter Study by Turkish Oncology Group (TOG). Cancers 0 41899520
2025 Treatment outcomes of sunitinib and/or pazopanib in advanced alveolar soft part sarcoma: A Turkish Oncology Group (TOG) study. Scientific reports 0 41315659
2025 Real-World Experience with Non-Metastatic Male Breast Cancer: A 222-Patient Multicenter Study from the Turkish Oncology Group (TOG). Cancers 0 41463146

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